A liquid chromatograph mass spectrometer (LC/MS) comprises a liquid chromatograph unit (LC unit) for separating liquid specimen into its components and discharging the liquid specimen according to its components, an ionization chamber (interface unit) for ionizing the specimen components that are discharged from the LC unit and a mass spectrometer (MS unit) for detecting ions that are introduced from the ionization chamber. Various ionization methods are used for the ionization of liquid specimen in an ionization chamber, but atmospheric pressure ionization such as atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) are often used.
Specifically, with atmospheric pressure chemical ionization, the tip of a nozzle that is connected to the end of a column of an LC unit is disposed in a direction pointing towards the interior of the ionization chamber, and a probe electrode is disposed in front of the nozzle tip. Droplets of the specimen that are atomized by heating at the nozzle are ionized by chemical reaction with carrier gas ions (buffer ions) that are generated by corona discharge from the probe electrode. With electrospray ionization, the tip of a nozzle that is connected to the end of a column of an LC unit is disposed in a direction pointing towards the interior of an ionization chamber, and a high voltage of approximately several kV is applied to the nozzle tip to generate a strong unequal electrical field. The electrical field causes the liquid specimen to separate according to its charge due to Coulomb attraction and atomize. When the specimen droplets come into contact with ambient air, the solvent in the specimen droplets evaporates, and gas ions are generated.
With atmospheric pressure chemical ionization and electrospray ionization, liquid specimens are ionized at near atmospheric pressure while the ionization chamber is kept at a high pressure (i.e., close to atmospheric pressure) and the mass spectrometer unit is kept at a low pressure (i.e., a high degree of vacuum). To maintain a pressure differential between the ionization chamber and the mass spectrometer unit, intermediate chambers and the like are disposed between the ionization chamber and the mass spectrometer unit with the degree of vacuum of the intermediate chambers being gradually increased. (See for example Patent Literature 1.)
FIG. 6 shows a schematic view of the configuration of one example of a liquid chromatograph mass spectrometer that uses electrospray ionization. FIG. 7 and FIG. 8 show perspective views of the ionization chamber shown in FIG. 6. FIG. 5 shows a detailed view of the spray unit. FIG. 7 shows the ionization chamber with its door closed. FIG. 8 shows the ionization chamber with its door opened.
The liquid chromatograph mass spectrometer includes an ionization chamber 11 comprising a chamber (enclosure) 210, a first intermediate chamber 12 located adjacent to the ionization chamber 11, a second intermediate chamber 13 located adjacent to the first intermediate chamber 12 and a mass spectrometry chamber (MS unit) 14 located adjacent to the second intermediate chamber 13. These chambers are formed in succession and are each separated by a partition wall.
The liquid specimen that is separated into its components by the liquid chromatograph unit is supplied to the ionization chamber via flow path 155. Nebulized gas (nitrogen gas) is provided through flow path 156. The liquid specimen and the nebulized gas are supplied to spray (probe) 15 from where they are sprayed.
FIG. 5(a) shows a side view of the spray unit. FIG. 5(b) shows an enlarged sectional view of part A shown in FIG. 5. The spray unit 15 has a double-walled tubular structure. The liquid specimen that is supplied through flow path 155 is discharged from the inner side of the tube 159. The nitrogen gas that is supplied through flow path 156 is discharged through the space between the tube 159 and nozzle 152 that has a tubular shape. This arrangement results in the discharged liquid specimen to collide with nebulized gas that is discharged around the tube 159 and to atomize as it is sprayed.
Furthermore, a voltage source (not illustrated) is wired (not illustrated) to apply a high voltage of several kV to the tip of nozzle 152 to cause ionization.
In FIG. 5 through FIG. 8, spray unit 15 is used for electrospray ionization. The spray unit 15 is usually removably attached to the chamber 210. If the use of atmospheric pressure chemical ionization is desired, the spray unit 15 is removed and replaced on the chamber 210 by a unit with an integrated probe electrode for discharging purposes.
A position adjustment knob (not illustrated) is provided so that the tip of the spray unit 15 can engage in a substantially parallel movement over a predetermined range on a y-z plane that is orthogonal to the x-axis. After the position is suitably adjusted, the position of the tip of the spray unit is fixed using a position fixing knob. The spray unit 15 can also be pushed in and pulled out of the spray unit itself in the x-axis direction (so that the amount of protrusion dx can be adjusted). After the position is suitably adjusted, a nut (not illustrated) is used to fix the position.
The ionization chamber 11 includes a chamber 210 in the shape of a rectangular solid measuring 13 cm×13 cm×12 cm. The chamber 210 comprises a first wall surface (upper surface) 210a, a second wall surface (partition wall) 210b, a third wall surface (front surface) 210c, a fourth wall surface (right side surface) 210d, a fifth wall surface (left side surface) 210e and a sixth wall surface (lower surface) 210f. The internal space of the ionization chamber 11 is thus formed and enclosed by the upper surface 210a, partition wall 210b, front surface 210c, right side surface 210d, left side surface 210e and the lower surface 210f. 
A circular opening 11a is formed in the upper surface 210a to provide a connection in the vertical direction. The spray unit 15 is installed in the opening 11a from above.
The partition wall 210b is provided to form a partition between the interior of the ionization chamber 11 and the interior of the first intermediate chamber 12. A heater block 20 with a temperature adjustment mechanism (not illustrated) incorporated therein is secured to the partition wall 210b. A solvent removal tube 19 having a tubular shape (outer diameter of 1.6 mm and inner diameter of 0.5 mm) is formed in the heater block 20 so that the interior of the ionization chamber 11 and the interior of the first intermediate chamber 12 are connected by the solvent removal tube 19. As fine droplets of the specimen and ions that are sprayed by the spray unit 15 pass through the solvent removal tube 19, the heating and collision provide the effect and function of promoting ionization and removing the solvent.
The inlet to the solvent removal tube 19 is oriented in a direction substantially perpendicular to the specimen spraying direction of the spray unit 15 so that large droplets of the specimen that are sprayed do not directly enter the solvent removal tube 19. A drain 30 is formed on the lower surface 2101 in front of the specimen spraying direction of the spray unit 15 so that unnecessary specimen is discharged out through the drain 30.
A first ion lens 21 is disposed in the first intermediate chamber 12. An exhaust opening 31 which uses an oil rotary pump (RP) to create a vacuum for exhausting purpose is disposed on the lower surface of the first intermediate chamber 12. A skimmer 22 having an orifice is formed in the partition wall between the first intermediate chamber 12 and the second intermediate chamber 13. The orifice connects the interior of the first intermediate chamber 12 and the interior of the second intermediate chamber 13.
An octupole 23 and a focal lens 24 are disposed in the second intermediate chamber 13. An exhaust opening 23 through which exhausting is performed by a vacuum created by a turbo molecular pump (TMP) is disposed on the lower surface of the second intermediate chamber 13. An incoming lens 25 having an orifice is disposed in the partition wall between the second intermediate chamber 13 and the mass spectrometry chamber 14. The interior of the second intermediate chamber 13 and the interior of the mass spectrometry chamber 14 are connected by the orifice.
A first quadrupole 16, second quadrupole 17 and detector 18 are disposed in the mass spectrometry chamber 14. An exhaust opening 33 through which exhausting is performed by a vacuum created by a turbo molecular pump (TMP) is disposed on the lower surface of the mass spectrometry chamber 14.
The ion lens 21, octupole 23, focal lens 24 and the incoming lens 25 are each at some level of vacuum and provide a converging effect for efficiently sending to the next stage the ions that pass through them at particular speeds.
In a liquid chromatograph mass spectrometer such as the afore-described, the ions that are generated in the ionization chamber 11 are sent to the mass spectrometry chamber 14 via the solvent removal tube 19, first ion lens 21 in the first intermediate chamber 12, skimmer 22, octupole 23 and focal lens 24 in the second intermediate chamber 13 and incoming lens 25. After unnecessary ions are discharged by quadrupoles 16 and 17, only specific ions which reach detector 18 are detected.
The ion generation efficiency of ionization chamber 11 when using electrospray ionization can be increased by appropriately adjusting the positional relationship between the spray unit 15 which sprays the liquid specimen and the inlet of the solvent removal tube 19, by ensuring that the spray unit 15 is providing a normal spray, and by checking to keep the spray unit 15 clean. Performing such adjustments or check is facilitated if the interior of the ionization chamber 11 can be observed from the outside and the interior of the ionization chamber 11 opened. For this reason, with the liquid chromatograph mass spectrometer, a substantially square-shaped opening 11b (11 cm×11 cm) and a rectangular flat door 150 (18 cm×15 cm×2.5 cm) for covering opening 11b are formed on the front surface 210e. A rectangular observation window 151 (11 cm×8 cm) made of glass and the like is formed in the center of the door 150.
The door 150 opens and closes on hinges 52 pivoting about a first edge (left edge) 150a of a rectangular door. This allows a person performing the measurements to freely open and close the door 150 leading to the interior of the ionization chamber 11. So that the door 150 securely closes the opening 11b during measurements, an opening is formed at the lower right area of the door 150 where a screw can be inserted in the fore-to-aft direction. A person performing measurements inserts a male screw 154 from the front into the screw opening so as to engage with a screw hole 155 that is formed in the lower right area of the front surface 210c. This disables the door 150 from being opened or closed.
The door 150 has a laminated construction featuring a heat-resistant metallic cover, a metallic main body and a rubber O-ring 56 which are layered in this sequence starting from the front side.